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哮喘药物研发进展:评估鼻细胞采样及其他方法的潜力。

Advances in asthma drug discovery: evaluating the potential of nasal cell sampling and beyond.

机构信息

IRCCS, San Raffaele Pisana Hospital, Department of Pulmonary Rehabilitation , Rome , Italy.

出版信息

Expert Opin Drug Discov. 2014 Jun;9(6):595-607. doi: 10.1517/17460441.2014.909403. Epub 2014 Apr 22.

DOI:10.1517/17460441.2014.909403
PMID:24749518
Abstract

INTRODUCTION

Inhaled corticosteroid anti-inflammatory therapy is effective at controlling disease symptoms of asthma, but a subset of patients remains symptomatic despite optimal treatment, creating a clear unmet medical need. Moreover, none of the currently available drugs for asthma are really disease-modifying or curative. Although murine models of asthma, based on transgenic and knockout animals, may offer an integrated pathophysiological system for studying the characteristics of airway inflammation and hyperresponsiveness, these alterations are noteworthily different compared with those observed in asthmatic patients. Since a clear functional and inflammatory relationship between the nasal mucosa and bronchial tissue in patients suffering from asthma and allergic rhinitis has been recognized, using preclinical models based on human nasal cells sampling might support a prompt and effective anti-inflammatory drug discovery in asthma.

AREAS COVERED

The authors provide a review, which discusses the potential role of nasal cell sampling and its application in advanced drug discovery for asthma. The contents range from the similarities and differences between asthma and allergic rhinitis up to artificial airway models based on sophisticated human lung-on-a-chip devices.

EXPERT OPINION

Nasal cell sampling and processing have reached a great potential in asthma drug discovery. The authors believe that models of asthma, which are based on human nasal cells, can provide valuable indications of proof of pharmacological and potential therapeutic efficacy in both preclinical and early clinical settings.

摘要

简介

吸入皮质类固醇抗炎疗法可有效控制哮喘的疾病症状,但仍有一部分患者即使接受最佳治疗仍存在症状,这表明存在明确的未满足的医疗需求。此外,目前用于哮喘的药物均不能真正地改变疾病进程或根治疾病。虽然基于转基因和基因敲除动物的哮喘小鼠模型可能为研究气道炎症和高反应性的特征提供一个综合的病理生理学系统,但这些改变与哮喘患者观察到的改变明显不同。由于已经认识到哮喘和变应性鼻炎患者的鼻黏膜和支气管组织之间存在明确的功能和炎症关系,因此使用基于人类鼻细胞采样的临床前模型可能有助于快速有效地发现哮喘的抗炎药物。

涵盖领域

作者对鼻细胞采样及其在哮喘药物研发中的应用进行了综述,内容涉及哮喘和变应性鼻炎的异同,以及基于复杂的人肺芯片设备的人工气道模型。

专家意见

鼻细胞采样和处理在哮喘药物发现方面具有巨大潜力。作者认为,基于人鼻细胞的哮喘模型可以在临床前和早期临床环境中提供有价值的药理学和潜在治疗疗效的证据。

相似文献

1
Advances in asthma drug discovery: evaluating the potential of nasal cell sampling and beyond.哮喘药物研发进展:评估鼻细胞采样及其他方法的潜力。
Expert Opin Drug Discov. 2014 Jun;9(6):595-607. doi: 10.1517/17460441.2014.909403. Epub 2014 Apr 22.
2
Allergic rhinitis and asthma: more similarities than differences.变应性鼻炎和哮喘:相似之处多于不同之处。
Allerg Immunol (Paris). 2001 Jun;33(6):237-41.
3
Emerging drugs for asthma.哮喘的新型药物
Expert Opin Emerg Drugs. 2008 Dec;13(4):643-53. doi: 10.1517/14728210802591378.
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Upper and lower airway pathology in young children with allergic- and non-allergic rhinitis.患有过敏性和非过敏性鼻炎的幼儿的上、下气道病理学
Dan Med Bull. 2011 May;58(5):B4278.
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Small-molecule anti-inflammatory drug compositions for the treatment of asthma: a patent review (2013 - 2014).用于治疗哮喘的小分子抗炎药物组合物:专利综述(2013 - 2014年)
Expert Opin Ther Pat. 2015 Jul;25(7):743-54. doi: 10.1517/13543776.2015.1041923. Epub 2015 May 14.
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Methods used in clinical development of novel anti-asthma therapies.新型抗哮喘疗法临床开发中使用的方法。
Respir Med. 2008 Mar;102(3):332-8. doi: 10.1016/j.rmed.2007.10.018. Epub 2007 Dec 3.
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Geniposide inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma.栀子苷抑制哮喘小鼠模型中的气道炎症和气道高反应性。
Int Immunopharmacol. 2013 Nov;17(3):561-7. doi: 10.1016/j.intimp.2013.06.028. Epub 2013 Jul 13.
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[Status of leukotrienes in the pathophysiology of asthma. Necessity for antileukotrienes treatment].[白三烯在哮喘病理生理学中的地位。抗白三烯治疗的必要性]
Pneumonol Alergol Pol. 2010;78(1):68-73.
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Tiarellic acid attenuates airway hyperresponsiveness and inflammation in a murine model of allergic asthma.替拉珠利酸可减轻变应性哮喘小鼠模型的气道高反应性和炎症。
Int Immunopharmacol. 2012 Jan;12(1):117-24. doi: 10.1016/j.intimp.2011.10.021. Epub 2011 Nov 12.
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Relation between inflammation and symptoms in asthma.哮喘中炎症与症状的关系。
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